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. 2022 May;126(9):1301-1309.
doi: 10.1038/s41416-021-01697-z. Epub 2022 Jan 14.

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Trasias Mukama  1 , Renée Turzanski Fortner  1 , Verena Katzke  1 , Lucas Cory Hynes  1 , Agnese Petrera  2 , Stefanie M Hauck  2 , Theron Johnson  1 , Matthias Schulze  3   4 , Catarina Schiborn  3 , Agnetha Linn Rostgaard-Hansen  5 , Anne Tjønneland  5 , Kim Overvad  6 , María José Sánchez Pérez  7   8   9   10 , Marta Crous-Bou  11   12 , María-Dolores Chirlaque  9   13 , Pilar Amiano  9   14   15 , Eva Ardanaz  9   16   17 , Eleanor L Watts  18 , Ruth C Travis  18 , Carlotta Sacerdote  19 , Sara Grioni  20 , Giovanna Masala  21 , Simona Signoriello  22 , Rosario Tumino  23 , Inger T Gram  24 , Torkjel M Sandanger  24 , Hanna Sartor  25 , Eva Lundin  26 , Annika Idahl  27 , Alicia K Heath  28 , Laure Dossus  29 , Elisabete Weiderpass  30 , Rudolf Kaaks  31
Affiliations

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Trasias Mukama et al. Br J Cancer. 2022 May.

Abstract

Background: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer.

Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer.

Results: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9-18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone.

Conclusion: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0-9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Distributions of protein biomarker levels in controls, and in ovarian cancer.
Each of the panels shows marker distributions in the form of Box plots, for biomarkers that yielded an AUC ≥ 0.7 for ovarian cancer diagnosis 0–9 months after blood draw. For the cancer cases, the plots show marker distributions measured in blood samples that had been collected 0–9 or >9–18 months prior to diagnosis.
Fig. 2
Fig. 2. ROC plots for top biomarkers individually and in combination with CA125, by lag-time.
Top row (a) shows the performance of individual biomarkers. Bottom row (b) shows the performance of the biomarkers when combined with CA125.
See this image and copyright information in PMC

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